32578_Management of DVT

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    Management of DVT

    Soheir Adam, MD, MSC, FRCPath

    Asst. Professor & Consultant

    Hematologist KAU

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    VTE

    Incidence of VTE 2-3 per 1000

    Incidence is higher in men than in

    women ( above the age of 45).Overall adjusted incidence in men is

    130 : 100,000 vs 110: 100,000 inwomen(1.2:1)

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    VTE

    DVT and PE are a single clinical entity

    Risk of early death in DVT + PE is 18 X higherthan in DVT alone

    of PE cases present with sudden death

    Other predictors of poor survival in DVT areolder age, male gender, confinement tohospital, CHF, chronic lung disease,neurological disease and active malignancy.

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    3. Thrombus formation in the left auricle

    (computer graphics superimposed on in-body

    photograph)

    The irregular beating of the heart in atrial fibrillation

    creates ideal conditions for thrombus formation in the

    left auricle, especially in patients with mitral valve

    insufficiency.

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    5. Fragmentation of the thrombus

    (computer graphics superimposed on in-body

    photograph)

    As the size of the thrombotic mass increases, it

    becomes more of a threat. Especially if the heart rate is

    normalised, fragments of the thrombus may break away

    to be swept into the circulation.

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    PE

    Predictors of poor survival in PE:

    Syncope

    Arterial hypotensionRight sided HF ( clinically or by plasma

    markers levels or echocardiography)

    These should receive aggressiveanticoagulation +/- thrombolytic therapy.

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    11. Diagnosis of pulmonary embolism

    (perfusion and ventilation scans)

    In another patient with pulmonary embolism,a perfusion scan shows that an embolus hasstopped the blood flow to part of one lung.The ventilation scan shows that this area

    is ventilated normally.

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    Long Term Complications of

    VTERecurrence

    PTS

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    Complications of VTE

    1. Recurrence

    Prandoni et al found the risk aftercessation of anticoagulation 24.8% at 5years and 30.3% at 8

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    14. Ref: Schulman S et al. The duration of oral anticoagulant therapy after asecond episode of venous thromboembolism. The Duration of Anticoagulation

    Trial Study Group. N Engl J Med 1997;336:393-8Short-term primary prevention of deep vein thrombosis/pulmonary embolism withanticoagulant therapy is today common practice for patients undergoing orthopaedicsurgical procedures. Patients with confirmed deep vein thrombosis, irrespective of theunderlying cause, typically receive anticoagulant treatment for 3 to 6 months, dependingon the location of the thrombosis and on other risk factors that the patient may have.

    For pulmonary embolism the duration of treatment is often 6 months. However, theoptimal length of therapy is the subject of debate. Patients are at increased risk ofsuffering from a new episode of venous thromboembolism once anticoagulant therapyis completed. The next embolus may well prove to be fatal. There is a marked differencein the cumulative probability of a new episode of venous thromboembolism between thepatients receiving indefinite treatment and those in the 6-month group.

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    Complications of VTE

    Risk of recurrence increased with

    Male gender

    Increased age

    Increased BMI Neurological disease

    Paresis

    Active malignancy

    Idiopathic VTE

    APS Prt C,S and AT deficiency

    Persistent residual DVT

    Consider pro longed 2ry proph ylaxis in the above

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    Complications of VTE

    Factors not predictive of recurrence:

    VTE in pregnancy, CCP and gynecologicalsurgery

    Recent surgery, trauma or fracture.

    Recent immobilzation

    Hormonal therapy (Tamoxifen)

    Failed prophylaxis Distal DVT, deep muscular DVT

    Short term oral ant icoagulat ion considered

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    Recurrent PE

    Risk of 7 day case mortality is significantly higher(34%) in recurrent PE, compared to recurrent

    DVT(4%) aloneConsider prolonged anticoagulation, especially if

    compromised cardiopulmonary functions

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    Complications of DVT

    2- Post- thrombotic syndrome

    Develops in 20- 30% of DVT

    Valvular damage or scarring leading toincompetence / residual venous obstruction dueto incomplete clearance

    Systemic thrombolytic therapy wasnt found to

    reduce incidence of PTS. Catheter- directed thrombolysis may hold

    potential but not recommended routinely.

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    Complications of DVT

    Risk factors for PTS

    Inadequate initial anticoagulation

    Recurrent DVTHigher BMI

    Distal vein thrombosis

    Recently, persistently elevated D- dimersNot impact for long term anticoagulation.

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    Impact of PTS

    In the US $ 200,000,000 annually totreat PTS and 2 million work days lost

    In Sweden its 75% of cost of DVT ttt In developing world major morbidity

    Poorer QOL

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    16. Post-thrombotic syndrome; leg ulcer

    Considerable numbers of patients suffer from post-thromboticsyndromes with, in severe cases, leg ulcers. Venousthromboembolism is an underestimated disease with hugesocio-economic implications.

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    Management of VTE

    Aim of Management:

    Initially : to prevent propagation of

    thrombusChronic anticoagulation to allow

    fibrinolysis and recanalization.

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    Management of VTE

    Heparin immediately and for at least 5days

    VKA started on the 1st day Failure to achieve optimum treatment

    early on leads to recurrence rates of

    20 %

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    Haemostasis: generation of thrombin and clot formation

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    Management of VTE

    UFH vs. LMWH

    Pros:

    Similar efficacy &superior safety

    Monitoring

    Risk of bleeding (lower risk in LMWH 1.3% vs.2.1%, odds ratio 0.60, meta-analysis of 14 studies)

    Lower overall mortality ( cancer pts.)

    Outpatient management

    Overall cost

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    Table 1 Recurrent symptomatic venous thromboembolism (VTE), major bleeding and mortality at

    3 months summary of two meta-analyses in deep vein thrombosis and pulmonary embolism

    Low molecular weight

    heparin (%)

    Unfractionated

    heparin (%)

    OR (95% CI)

    Deep vein thrombosis

    Recurrent VTE 86/1998 (4.3) 113/2021 (5.6) 0.75 (0.551.01)

    Major bleeding 30/2353 (1.3) 51/2401 (2.1) 0.60 (0.390.93)

    Mortality 135/2108 (6.4) 172/2137 (8.0) 0.78 (0.620.99)

    Pulmonary embolism

    Recurrent VTE 30/988 (3.0) 39/895 (4.4) 0.68 (0.421.09)

    Major bleeding 14/1023 (1.4) 21/928 (2.3) 0.67 (0.361.27)

    Mortality 46/988 (4.7) 55/895 (6.1) 0.77 (0.521.15)

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    Management of VTE

    LMWH

    Cons

    Reversal in bleeding patients: only the ATactivity, not the Xa is neutralized

    Obese patients: adjusted vs. total bodyweight

    Renal failure

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    Indirect thrombin inhibition

    Heparin/antithrombin/thrombin complex

    Heparin

    Antithrombin

    Thrombin

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    Management of PE

    UFH gradually replaced by LMWH

    Similar efficacy and safety in sub-

    massive PENo difference in mortality between

    altepase and LMWH compared toLMWH alone (NEJM 2002)

    Thrombolytic therapy essential inmassive PE (better identification ofpatients needed).

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    Table 2 Subgroup analysis of trials that included major (hemodynamically unstable) pulmonary embolismcompared with those that excluded patients with major pulmonary embolism

    Outcome

    Trials that included patients with major

    PE

    Trials that excluded patients with

    major PE

    Lysis, n/N

    (%)

    Heparin,

    n/N(%)

    OR (95% CI) Lysis,

    n/N(%)

    Heparin,

    n/N(%)

    OR (95% CI)

    Recurrent

    PE or death

    12/128

    (9.4)

    24/126

    (19.0)

    0.45 (0.22

    0.92)

    13/246

    (5.3)

    12/248

    (4.8)

    1.07 (0.50

    2.30)

    Recurrent

    PE

    5/128 (3.9) 9/126 (7.1) 0.61 (0.23

    1.62)

    5/246

    (2.0)

    7/248 (2.8) 0.76 (0.28

    2.08)

    Death 8/128 (6.2) 16/126

    (12.7)

    0.47 (0.20

    1.10)

    8/246

    (3.3)

    6/248 (2.4) 1.16 (0.44

    3.05)

    Major

    bleeding

    28/128

    (21.9)

    15/126

    (11.9)

    1.98 (1.00

    3.92)

    6/246

    (2.4)

    8/248 (3.2) 0.67 (0.24

    1.86)

    Wan et al, Circulat ion 2004.

    Thrombolytic Therapy in PE

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    Outpatient Management of

    DVT

    Hospital admissions

    Reduce the length of waiting time in A/E Pressure on hospital beds

    Cost issues

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    Exclusion Criteria

    Co- existent serious medical pathology

    Severe acute venous obstruction

    Patients in significant pain Renal impairment creatinine > 200 mol/l

    Liver disease

    Communication problems

    Poor social background Limited mobility

    Active bleeding

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    Exclusion Criteria

    High risk of bleeding

    Active peptic ulcer Uncontrolled hypertension ( diastolic> 110mmHg,

    systolic >200mmHg)

    Angiodysplasia

    Recent CNS or eye surgery Recent hemorrhagic stroke

    Thrombocytopenia ( plts < 100 X109/ L)

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    Clinical Assessment for DVT

    Suitable for OutpatientManagement

    Yes No

    DVT confirmed

    Patient analgesia

    Support stocking

    Medical assessment

    Need for medical follow- up

    Refer to hemostasis nurse

    Anticoagulant treatment

    Liaise with general practitioner

    Yes No

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    Outpatient Diagnosis

    No undue delay

    Validated clinical probability scores and

    3rd

    generation D- dimer assays If indicated then radiological

    investigations will follow ( vacant slots forA/E )

    Diagnosis usually responsibility ofmedical team, A/E team

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    Clinical Prediction Rule

    Entire leg tenderness along deep veins

    Collateral superficial veins

    Entire leg swelling

    Calf swelling >3 cm difference Dilated superficial veins

    Pitting edema

    Recent bed ridden >3 days

    Major surgery within last 3 ms.

    Active cancer within last 6 mo. Plaster

    Paralysis

    Presence of alternative Diagnosis

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    Imberti et al, 2006

    Journal of Thrombosis

    & Haemostasis

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    Outpatient Management

    Under auspices of HematologyDepartment

    One of several scenarios Daily OPD attendance

    District nurse or outreach hemostasisnurse

    LMWH administered by GP

    Administered by patient or relative

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    Lines of Accountability inOutpatient Management of DVT

    Diagnostic team

    Investigation of initial DVT/ PE

    Investigation of recurrent DVT/PE Patient analgesia

    Assessment for ambulatory care

    Formal medical assessmentMedical follow- up

    Liaison with GP

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    Lines of Accountability inOutpatient Management of DVT

    Treatment team

    Administration of outpatient care

    program Support stockings

    Patient education

    Thrombophilia testingAnticoagulant therapy

    Liaison with GP

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    Vitamin K Antagonists

    > reduction of risk of recurrence

    Bleeding risk is 1.4% per year of major

    bleeds 0.25% of fatal bleeds per year

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    Vitamin K Antagonists

    Inhibits Vitamin K dependentcarboxylase activity

    Prevents reduction of Vitamin K

    Humans secrete des--carboxyglutamicacid, an inactive protein

    Does not affect proteins already

    synthesizedMonitoring

    Multiple interactions with other drugs

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    Duration of Anticoagulation

    Plan designed clearly for each patientindividually at the start of anticoagulation

    Long term treatment of deep vein thrombosis (DVT) and pulmonary

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    Long-term treatment of deep vein thrombosis (DVT) and pulmonary

    embolism (PE)*

    Patient categories Dru

    g

    Duration

    (months)

    Comments

    First episode of DVT or PEsecondary to a transient

    (reversible) risk factor

    VKA

    3 Recommendation applies to bothproximal and calf vein thrombosis

    First episode of idiopathic DVT or

    PE

    VK

    A

    612 Continuation of anticoagulant

    therapy after 612 months may be

    considered

    First episode of DVT or PE and

    cancer

    LM

    WH

    36 Continuation of LMWH is

    recommended indefinitely or until

    the cancer is resolved

    First episode of DVT or PE with a

    documented thrombophilic

    abnormality

    VK

    A

    612 Continuation of anticoagulant

    therapy after 612 months may be

    considered

    First episode of DVT or PE with

    documented antiphospholipid

    antibodies or two or more

    thrombophilic abnormalities

    VK

    A

    12 Continuation of anticoagulant

    therapy after 12 months may be

    considered

    VKA, vitamin K antagonist; LMWH, low molecular weight heparin.

    *Based on the Seventh ACCP Conference document (13).

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    Duration of

    ThromboprophylaxisIndef in i te ant icoagu lat ion recommended :

    Two or more spontaneous thromboses

    One spontaneous thrombosis in case of AT deficiency orthe APS

    One life- threatening thrombosis

    One spontaneous thrombosis at an unusual site

    One spontaneous thrombosis in the presence of multiplegenetic thrombophilia defects

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    BSH guidelines 2005

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    Prevention of Recurrent VenousThromboembolism (PREVENT)

    Closed in December 2002

    Low intensity Warfarin reduced the

    rate of recurrence by 60% compared toplacebo

    No increase in major bleedingcomplications

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    Management of Thrombophilia

    AT deficiency

    Some patients are resistant to Heparin

    AT conc hasnt been studied in a controlled trial

    as an alternative to Heparin

    AT conc. can be used safely and effectively inAT deficiency and

    Acute severe VTE

    Difficulty to achieve adequate anticoagulation

    Recurrent thrombosis despite adequateanticoagulation

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    Protein C Deficiency

    Oral anticoagulation started under cover ofHeparin

    Dose of OAC should be gradually increased

    from 2mg for 3/7 until desired INR is reached

    WISN is an uncommon complication due to atransient hypercoagulable status

    Protein C conc. Can be used for prophylaxis

    against recurrent skin necrosis

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